Colon or rectal stent positioning for advanced cancer influences quality of life: a critical point of view

Background/Aim: Endoluminal self-expanding metallic stents (SEMS) may overcome the risk of mortality and morbidity of acute intestinal obstruction because of stage IV colon (CC) or rectal (RC) cancer. We evaluated the QoL in these groups of patients. Patients and Methods: Forty-eight patients were enrolled in a prospective longitudinal cohort single-center trial to undergo SEMS positioning. Twenty-five patients had a CC and 23 RC. Karnofsky performance scale, Visual Analogue Scale and the EQ-5D- 5LTM questionnaire were administered before treatment and at 1, 3 and 6 months. Results: Harmonized to the Italian population, the index values showed a statistically significant deterioration of the QoL in patients with RC when compared to those with CC at 1-, 3- and 6-months (1 month: p=0.001; 3- month: p=0.001; 6-month: p=0.045). Similarly, Visual Analogue Scale showed variations at 1- (p=0.008), 3- (p=0.001) and 6-months (p=0.020). Rectal stent deployment was the only independent predictor for a worse QoL in all domains (p<0.017; OR=0.196; 95%CI=0.51-0.749). Conclusion: Patients affected with stage IV CC had a better QoL after SEMS placement when compared to those affected with RC. The persistency of the primary tumor at the rectal level, even if irradiated, might negatively affect QoL

Orbital Kondo effect in carbon nanotubes

Progress in the fabrication of nanometer-scale electronic devices is opening new opportunities to uncover the deepest aspects of the Kondo effect, one of the paradigmatic phenomena in the physics of strongly correlated electrons. Artificial single-impurity Kondo systems have been realized in various nanostructures, including semiconductor quantum dots, carbon nanotubes and individual molecules. The Kondo effect is usually regarded as a spin-related phenomenon, namely the coherent exchange of the spin between a localized state and a Fermi sea of electrons. In principle, however, the role of the spin could be replaced by other degrees of freedom, such as an orbital quantum number. Here we demonstrate that the unique electronic structure of carbon nanotubes enables the observation of a purely orbital Kondo effect. We use a magnetic field to tune spin-polarized states into orbital degeneracy and conclude that the orbital quantum number is conserved during tunneling. When orbital and spin degeneracies are simultaneously present, we observe a strongly enhanced Kondo effect, with a multiple splitting of the Kondo resonance at finite field and predicted to obey a so-called SU(4) symmetry.Comment: 26 pages, including 4+2 figure

Non-pharmacological treatment for chronic obstructive pulmonary disease.

Evidence-based guidelines on treatment of patients with Chronic Obstructive Pulmonary Disease (COPD) have recently been developed. Non-pharmacological therapy of COPD has been receiving more interest and has been evolving rapidly in the last decade as an essential part of COPD treatment. In fact, non-pharmacological treatment is a complementary approach mainly in the advanced stages of COPD. Most of these care options appear to benefit patients in terms of quality of life and cost-effectiveness. The aim of the present review is to survey the most important non-pharmacological treatments for COPD (smoking cessation, rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation, and surgery) and their usefulness based on the currently available evidence. This review is based on an evaluation of the literature using a multimethod approach. A computerized MEDLINE search from 1966 through June 2003 was undertaken using the search terms pulmonary rehabilitation, surgery, smoking cessation, respiratory insufficiency/failure, and lung disease/obstructive. Non pharmacological treatment of COPD is a real option to successfully treat these patients and prevent further deterioration. All the included therapies are based on actual scientific evidence for patient benefits. To date, smoking cessation, comprehensive rehabilitation and long-term oxygen therapy are widely accepted as therapies which may positively impact the long-term management of COPD patients

Design, synthesis and evaluation of 3,4-dihydroxybenzoic acid derivatives as antioxidants, bio-metal chelating agents and acetylcholinesterase inhibitors

Metal ions, especially copper, zinc and iron, play an important role in the neurodegeneration process because they can affect protein misfolding, leading to the formation of the amyloid deposits and oxidative stress leading to reactive oxygen species (ROS). Here we report the synthesis and evaluation as antioxidant and metal chelating agents of 3,4-dihydroxybenzoic acid derivatives. Synthesized compounds were tested by the 2,2-diphenyl-2-picrylhydrazyl (DPPH) method showing a radical scavenging ability (EC50¼0.093–0.118 mM) higher than Trolox used as reference. Furthermore, these compounds were able to bind both iron and copper, especially the iron (III), by the formation of hexa-coordinated complexes. Synthesized compounds were tested to evaluate their ability to inhibit acetyl- and butyryl-cholinesterase; the obtained results have demonstrated that they are selective inhibitors of AChE (KI=1.5–18.9 uM) and result weakly active versus butyrylcholinesterase (BChE)

Activity of caffeic acid derivatives against Candida albicans biofilm

The aim of this study was to evaluate the caffeic acid (1) and ester derivatives (2-10) against Candida albicans biofilm and to investigate whether these compounds are able to inhibit the biofilm formation or destroy pre-formed biofilm. Caffeic acid ester 7, cinnamic acid ester 8 and 3,4-dihydroxybenzoic acid ester 10 are more active than fluconazole, used as reference drug, both on biofilm in formation with MIC50 values of 32, 32 and 16\u3bcg/mL, respectively, and in the early stage of biofilm formation (4h) with MIC50 values of 64, 32 and 64\u3bcg/mL, respectively. These esters result also more active than fluconazole on mature biofilm (24h), especially 8 and 10 with MIC50 values of 64\u3bcg/mL

Discovery of N-aryl-naphthylamines as in vitro inhibitors of the interaction between HIV integrase and the cofactor LEDGF/p75

A series of N-aryl-naphthylamines, exemplified by the structures 11-16, were chosen for an in-house library screening to assay their ability to disrupt the interaction between the LEDGF cofactor and the HIV integrase. Structure modification led also to design and synthesize new compounds 17a-f. Compounds 11e,h,k,n, 13b, and 14 showed good activity in AlphaScreen assay. The most active compound 11e (IC50 Combining double low line 2.5 μM) was selected for molecular modeling studies and showed a binding mode similar to the one of the known LEDGIN

Structure−activity relationship of pyrrolyl diketo acid derivatives as dual Inhibitors of HIV‑1 integrase and reverse transcriptase ribonuclease H domain

The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well as therapeutic costs. HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets for HIV-1 chemotherapy, and the identification of dual IN/RNase H inhibitors is an attractive strategy for new drug development. We newly synthesized pyrrolyl derivatives that exhibited good potency against IN and a moderate inhibition of the RNase H function of RT, confirming the possibility of developing dual HIV-1 IN/RNase H inhibitors and obtaining new information for the further development of more effective dual HIV-1 inhibitor

New Promising Compounds with in Vitro Nanomolar Activity against <i>Trypanosoma cruzi</i>

The antiparasitic activity of azole and new 4-aminopyridine derivatives has been investigated. The imidazoles <b>1</b> and <b>3</b>–<b>5</b> showed a potent in vitro antichagasic activity with IC₅₀ values in the low nanomolar concentration range. The (<i>S</i>)-<b>1</b>, (<i>S</i>)-<b>3</b>, and (<i>S</i>)-<b>5</b> enantiomers showed (up to) a thousand-fold higher activity than the reference drug benznidazole and furthermore low cytotoxicity on rat myogenic L6 cells

Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase

A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3′-processing. These strand transfer selective inhibitors also inhibited HIV-1 RNase H with low micromolar potencies. Molecular modeling studies based on both the HIV- 1 IN and RNase H catalytic core domains provided new structural insights for the future development of these compounds as dual HIV-1 IN and RNase H inhibitors